Hemodynamic Analysis Of The Pathogenesis Of Renal Vascualr Hypertension

Thestudy on thepathogenesis of renal vascular hypertension can raise the understanding of secondary hypertension, and help clinicians identify the cause and develop the treatment, which can significantly reduce the high mortality and disability caused by hypertension and its complications. In this thesis an integrated physiological computational modeling for cardiovascular system is developed by the combination of one-dimensional nonlinear fluid model in compliant vessels and the physiological regulation model. The model has been used to investigate the effect of renal artery stenosis on hemodynamics of arterial system and kidney filtration function with and without the regulation of renin-angiotensin system (RAS). The model consists of three modules:one-dimensional (1D) hemodynamic model of blood flow in arterial system, the model of glomerular network and the pressure regulation model of renin-angiotensin system.First, the1D hemodynamic model has been improved in the treatment of outlet boundary condition. The structure-tree model for small arteries has been built based on the principle of minimum work, from which the root impedance and total compliance was calculated to be the outlet boundary parameters of1D model. The advantage of this approachis to provide the outcomes of arteriole tree with any structure, and to avoid the problem effectively that the outlet parameters for1D models are hard to be estimated when the geometry of arteriole network changes. By coupled with zero-dimensional stenosis model, the1D model has been applied in the simulation of blood flow and oxygen transport in the generic and patient-specific models of the circle of Willis. The results correspond with the physiological features well, which demonstrates the availability of the1D model.Second, a lumped model of stenotic flow has been established based on the Lorentz reciprocal theorem and the voxel-based VOF (volume of fluid)3D simulator. The developed correlation indicates that the pressure drop of steady flow in the stenosis vessel can be decomposed into the pressure drop of Stokes flow, which can be obtained by modified lubrication theory, and the nonlinear terms caused by the stenosis geometry and the momentum transport, which is related to the stenosis severity and the Reynolds number. It is shown that the new lumped model has higher accuracy compared to Young and Tsai’s empirical relation.Finally, the mathematical model of RAS pressure regulation is established, and coupled with the hemodynamic model and the glomerular network model. In the RAS regulation model, the conservation equations of concentration of the active substances are derived by using the first order partial differential equations and the relation between the contraction rate of arteriolar radius and the angiotensin Ⅱ concentrations is represented with S-type function, from which the correlation of the total peripheral resistance and the Ang Ⅱ concentration is obtained. The integrated model is applied for the simulation of pressure variation in two-kidney, one clipped (2K1C) experiment. The analysis shows that, when there is no RAS regulation, the renal artery stenosis can lead to the decrease of kidney perfusion rate and perfusion pressure, and the descending rate increases with the deepening of stenosis severity. The glomerular filtration rate, which represents the function of kidney, decreases with the reduction of kidney perfusion pressure. When the stenosis severity of renal artery is up to85%, the glomerular filtration rate is reduced significantly and then falls rapidly to be zero as the stenosis severity increases to95%, while the perfusion pressure remains slightly above50mmHg. On the other hand, when RAS regulation is involved, the reduction of perfusion pressure caused by renal artery stenosis will activate the renin-angiotensin system. The renin concentration, the Ang Ⅱ concentration, and the total peripheral resistance will rise to a new balance point. The pressure of the stenosis renal artery will recovered with an amplification of13.5mmHg when the degree of stenosis is90%, and the feedback gain of pressure is1.2, which conforms to the physiological reference value (1-2).At the same time, pressures of other arteries will also rise due to the increase of total peripheral resistance, and then lead to hypertension. In summary, the integrated model withthecoupledcardiovascular and RAS system well simulated the pressure variation during one kidney clipped, which provides arevealing insight intothe relationship between blood pressure control and RAS regulation.